Scientists uncover genes that control embryonic stem cell fate

Washington, July 11 : Scientists at the University of California, San Francisco say that they have identified about two-dozen genes that control embryonic stem cell fate.

The researchers say that the genes may either prod or restrain stem cells from drifting into a kind of limbo, which lies between the embryonic stage and fully differentiated cells like bone, muscle or fat.

They believe that knowing the genes and proteins that control a cell's progress toward the differentiated form may help accelerate the process, and turn out to be a potential boon for the use of stem cells in therapy or the study of some degenerative diseases.

Describing their study in the journal Cell, the researchers have revealed that their finding comes from the first large-scale search for genes crucial to embryonic stem cells.

"The genes we identified are necessary for embryonic stem cells to maintain a memory of who they are. Without them the cell doesn't know whether it should remain a stem cell or differentiate into a specialized cell," says Dr. Barbara Panning, associate professor of biochemistry and biophysics at UCSF, and senior author on the paper.

During the study, the researchers used a powerful technique called RNA interference (RNAi) to screen more than 1,000 genes for their role in mouse embryonic stem cells.

With aid of the technique, the research team was able to "knock down" individual genes, reducing their abundance in order to determine the gene's normal role.

The researchers said that they focused their study on proteins that help package DNA.

According to them, DNA normally wraps around protein complexes called nucleosomes in the nucleus, forming a structure known as chromatin that makes up chromosomes.

Their efforts uncovered 22 proteins, each of which is essential for embryonic stem cells to maintain their consistent shape, growth properties, and pattern of gene expression.

The researchers say that most of the genes identified by them code for multi-protein complexes that physically rearrange (remodel) nucleosomes, changing the likelihood that the underlying genes will be expressed to make proteins.

They say that the main player is a 17-protein complex called Tip60-p400, which is necessary for the cellular memory that maintains embryonic stem cell identity.

Panning says that, without this complex, the embryonic stem cells turned into a different cell type, which had some features of a stem cell but many features of a differentiated cell.

The researchers are of the opinion that Tip60-p400 is necessary for embryonic stem cells to correctly read the signals that determine cell type.

They say that their findings are not only important for understanding cellular memory in embryonic stem cells, but will also likely be relevant to other cell types.

According to them, inactivation of other genes disrupted embryonic stem cell proliferation.

The team says that these genes were already known to have only slight influence on viability of mature cells in the body.

Based on their observations, the researchers came to the conclusion that embryonic stem cells are "uniquely sensitive to certain perturbations of chromatin structure."

Panning feels that, if other types of stem cells are also found to be sensitive to these chromatin perturbations, this could lead to novel cancer therapies in the future.

ANI